2013 Rustbelt RNA Meeting
The poly(A) binding protein C1 (PABPC1) is a highly conserved and ubiquitously expressed regulatory factor that plays a key role in mRNA polyadenylation, translation and stability. Here we report that PABPC1 protein expression in mice is tightly regulated during postnatal heart development. Western blot analyses showed a surprising 800-fold reduction in PABPC1 protein expression in heart within the first four weeks after birth. However, PABPC1 mRNA levels showed no more than five-fold decrease clearly indicating that the developmental decrease is largely post-transcriptional. We found that both during physiological and pathological cardiac hypertrophy conditions; there is a strong increase in expression of PABPC1 protein.
To investigate a direct role for PABPC1 in cardiac hypertrophy, we generated tetracycline-inducible and cardiac-specific PABPC1 transgenic mice. Histological and echocardiography studies from these mice demonstrate that re-expression of PABPC1 in adult heart was sufficient to induce cardiac hypertrophy without producing any functional or pathological defects. Importantly, PABPC1 depleted neonatal cardiomyocytes failed to exhibit isoproterenol induced hypertrophic growth. Taken together, these results strongly support an important role for PABPC1 in controlling gene regulation programs during normal heart development and in cardiac hypertrophy.
Keywords: PABPC1, Cardiac Hypertrophy, Devlopment